Dept of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
Dept of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Eur Respir J. 2019 Apr 18;53(4). doi: 10.1183/13993003.02237-2018. Print 2019 Apr.
A clinically useful model to prognose onset of respiratory insufficiency in amyotrophic lateral sclerosis (ALS) would inform disease interventions, communication and clinical trial design. We aimed to derive and validate a clinical prognostic model for respiratory insufficiency within 6 months of presentation to an outpatient ALS clinic.We used multivariable logistic regression and internal cross-validation to derive a clinical prognostic model using a single-centre cohort of 765 ALS patients who presented between 2006 and 2015. External validation was performed using the multicentre Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database with 7083 ALS patients. Predictors included baseline characteristics at first outpatient visit. The primary outcome was respiratory insufficiency within 6 months, defined by initiation of noninvasive ventilation, forced vital capacity (FVC) <50% predicted, tracheostomy, or death.Of 765 patients in our centre, 300 (39%) had respiratory insufficiency or death within 6 months. Six baseline characteristics (diagnosis age, delay between symptom onset and diagnosis, FVC, symptom onset site, amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R) total score and ALSFRS-R dyspnoea score) were used to prognose the risk of the primary outcome. The derivation cohort c-statistic was 0.86 (95% CI 0.84-0.89) and internal cross-validation produced a c-statistic of 0.86 (95% CI 0.85-0.87). External validation of the model using the PRO-ACT cohort produced a c-statistic of 0.74 (95% CI 0.72-0.75).We derived and externally validated a clinical prognostic rule for respiratory insufficiency in ALS. Future studies should investigate interventions on equivalent high-risk patients.
一种有助于预测肌萎缩侧索硬化症（ALS）患者呼吸功能不全发作的临床模型，将为疾病干预、沟通和临床试验设计提供信息。我们旨在开发和验证一种用于预测门诊就诊的 ALS 患者在 6 个月内发生呼吸功能不全的临床预后模型。
我们使用多变量逻辑回归和内部交叉验证，从 2006 年至 2015 年期间在单中心队列中纳入 765 名 ALS 患者，使用该模型推导临床预后模型。使用多中心资源开放获取肌萎缩侧索硬化症临床试验（PRO-ACT）数据库对该模型进行外部验证，该数据库包含 7083 名 ALS 患者。预测因子包括首次门诊就诊时的基线特征。主要结局为 6 个月内发生呼吸功能不全，定义为开始使用无创通气、用力肺活量（FVC）<预测值的 50%、行气管切开术或死亡。
在我们的中心，765 名患者中有 300 名（39%）在 6 个月内出现呼吸功能不全或死亡。6 个基线特征（诊断年龄、症状发作和诊断之间的延迟、FVC、症状发作部位、肌萎缩侧索硬化功能评定量表修订版（ALSFRS-R）总分和 ALSFRS-R 呼吸困难评分）用于预测主要结局的风险。该模型在推导队列中的 C 统计量为 0.86（95%CI 0.84-0.89），内部交叉验证产生的 C 统计量为 0.86（95%CI 0.85-0.87）。使用 PRO-ACT 队列对模型进行外部验证的 C 统计量为 0.74（95%CI 0.72-0.75）。
我们推导并外部验证了用于 ALS 呼吸功能不全的临床预后规则。未来的研究应该在具有同等高风险的患者中进行干预。
